ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.743G>T (p.Arg248Leu) (rs769166447)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580624 SCV000682415 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing
Invitae RCV000540986 SCV000622748 uncertain significance Ataxia-telangiectasia syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 248 of the ATM protein (p.Arg248Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with variant ataxia telangiectasia (PMID: 24120321). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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